PubMed Health⌕ Search

Biomedical subjects

Detlef H Krieter

Publications and source records attributed to Detlef H Krieter.

10 recordsLinked to original sources

Effects of a polyelectrolyte additive on the selective dialysis membrane permeability for low-molecular-weight proteins.

BACKGROUND: Improving the sieving characteristics of dialysis membranes enhances the clearance of low-molecular-weight (LMW) proteins and may have an impact on outcome in patients receiving haemodialysis. To approach this goal, a novel polyelectrolyte additive process was applied to a polyethersulphone (PES) membrane. METHODS: Polyelectrolyte-modified PES was characterized in vitro by measuring complement activation and sieving coefficients of cytochrome c and serum albumin. In a prospective, randomized, cross-over study, instantaneous plasma water clearances and reduction rates of LMW proteins [beta(2)-microglobulin (b2m), cystatin c, myoglobin, retinol binding protein] were determined in eight patients receiving dialysis treatment with PES in comparison with polysulphone (PSU). Biocompatibility was assessed by determination of transient leucopenia, plasma levels of complement C5a, thrombin-antithrombin III (TAT), myeloperoxidase (MPO) and elastase (ELT). RESULTS: PES showed a steeper sieving profile and lower complement activation in vitro compared with PSU. Instantaneous clearance (69 +/- 8 vs. 58 +/- 3 ml/min; P < 0.001) and reduction rate (72.3 +/- 1 5% vs 66.2 +/- 6.1%; P < 0.001) of b2m were significantly higher with PES as compared with PSU. With higher molecular weight of proteins, differences in the solute removal between PES and PSU further increased, whereas albumin loss remained low (PES, 0.53 +/- 0.17 vs PSU, <0.22 g/dialysis). MPO, ELT and TAT did not differ between the two membranes. In contrast, leucopenia was less pronounced and C5a generation was significantly lower during dialysis with PES. CONCLUSIONS: Polyelectrolyte modification of PES results in a higher LMW protein removal and in optimized biocompatibility. Whether these findings translate into better outcome of patients receiving haemodialysis requires further studies.

Animals↗

Beta(2)-microglobulin removal by extracorporeal renal replacement therapies.

There is increasing evidence that end-stage renal disease patients with lower beta(2)-microglobulin plasma levels and patients on convective renal replacement therapy are at lower mortality risk. Therefore, an enhanced beta(2)-microglobulin removal by renal replacement procedures has to be regarded as a contribution to a more adequate dialysis therapy. In contrast to high-flux dialysis, low-flux hemodialysis is not qualified to eliminate substantial amounts of beta(2)-microglobulin. In hemodialysis using modern high-flux dialysis membranes, a beta(2)-microglobulin removal similar to that obtained in hemofiltration or hemodiafiltration can be achieved. Several of these high-flux membranes are protein-leaking, making them suitable only for hemodialysis due to a high albumin loss when used in more convective therapy procedures. On-line hemodiafiltration infusing large substitution fluid volumes represents the most efficient and innovative renal replacement therapy form. To maximize beta(2)-microglobulin removal, modifications of this procedure have been proposed. These modifications ensure safer operating conditions, such as mixed hemodiafiltration, or control albumin loss at maximum purification from beta(2)-microglobulin, such as mid-dilution hemodiafiltration, push/pull hemodiafiltration or programmed filtration. Whether these innovative hemodiafiltration options will become accepted in clinical routine use needs to be proven in future.

Hemodiafiltration↗

Clinical cross-over comparison of mid-dilution hemodiafiltration using a novel dialyzer concept and post-dilution hemodiafiltration.

BACKGROUND: Several studies have indicated that the improved elimination of middle molecules by convective renal replacement procedures might be associated with a better outcome in end-stage renal disease (ESRD). On-line mid-dilution hemodiafiltration (HDF) with the Nephros OLpur MD 190 hemodiafilter represents a novel extracorporeal renal replacement therapy concept to increase the removal of middle molecules. METHODS: In a prospective cross-over study in 10 ESRD patients, this technique was compared to on-line post-dilution HDF with a conventional synthetic high-flux dialyzer, operated at its technical limit, concerning small and middle molecular solute removal. Each patient was treated 3 times for 4.0 +/- 0.4 hours with both filters. Blood flow was 400 mL/min, substitution flow (Q(S)) during mid-dilution HDF 200 mL/min, and during post-dilution HDF 100 mL/min, and effective dialysate flow of 700 - Q(S) mL/min. Instantaneous clearances, reduction ratios (RR), and middle molecule mass transfer in continuously collected dialysate were determined. RESULTS: While urea and creatinine clearances were significantly lower (6.4% and 3.9%, respectively), middle molecule removal was much more efficient in mid-dilution HDF over the whole range of investigated proteins: compared to post-dilution HDF, beta(2)-microglobulin (11.8 kD) clearance (165.8 +/- 26.59 vs. 201.9 +/- 20.63 mL/min; P < 0.001), RR (80.0 +/- 5.4% vs. 82.2 +/- 5.7%; P < 0.001), and dialysate mass transfer (53% higher; P < 0.001) were significantly higher. For the larger middle molecules, cystatin C (13.4 kD) and retinol-binding protein (21.2 kD), mid-dilution HDF resulted in an even more superior performance, indicated by significantly higher values of all investigated parameters. CONCLUSION: On-line mid-dilution HDF with the Nephros OLpur MD 190 hemodiafilter appears to be a true technologic step ahead in terms of improved middle molecule removal. This efficient procedure gives hope to play a role in preventing or at least retarding dialysis-related long-term complications, such as beta(2)m amyloidosis, in ESRD patients, and may contribute to a more adequate dialysis therapy.

Adult↗

Contact activation in low-density lipoprotein apheresis systems.

BACKGROUND: Anaphylactoid reactions due to contact activation have been observed in patients on ACE inhibitor therapy and hemodialysis with negatively charged dialysis membranes. Negatively charged surfaces are functional constituents of different LDL apheresis systems. Therefore, contact activation was investigated during LDL apheresis with three different systems: (i) heparin-induced extracorporeal LDL precipitation (HELP); (ii) dextran sulfate cellulose (DSC) columns; and (iii) modified polyacrylate gels (DALI) in a clinical setting. METHODS: 24 prevalent patients on regular LDL apheresis treatment were included in the study. Bradykinin, prekallikrein, and HMW kininogen were measured during a single LDL apheresis at different sites of the systems. RESULTS: LDL apheresis with DSC and DALI was associated with an extreme release of bradykinin after the passage of plasma or blood through the LDL adsorbers as well as with a decrease of prekallikrein and HMW kininogen during the course of the treatment. Bradykinin release exceeded the degradation capacity of the kininase II, since markedly elevated bradykinin concentrations were observed in the arterial line of the extracorporeal circuits of both systems. This was not associated with anaphylactoid reactions. In contrast to the treatments with DSC and DALI, the HELP system did not lead to any activation of the kallikrein-kinin system. CONCLUSION: From our data we conclude that angiotensin converting enzyme (ACE) inhibitors are contraindicated in patients on LDL apheresis with the DSC and the DALI system. Because the HELP system does not activate the kallikrein-kinin system, patients who need ACE inhibitors are predisposed for this LDL apheresis procedure.

Acrylic Resins↗

Mid-dilution on-line haemodiafiltration in a standard dialyser configuration.

BACKGROUND: Mid-dilution haemodiafiltration (HDF) results in an improved middle molecule removal compared with standard HDF. The OLpur MD 190 haemodiafilter represents a new dialyser design exclusively for mid-dilution on-line HDF. Compared with standard haemodialysers, structural changes in the headers allow the infusion of high replacement fluid volumes after a first post-dilution and before a second pre-dilution stage. METHODS: We compared in vitro the new device [blood flow (QB) 400 ml/min, substitution flow (QS) 100 and 200 ml/min, dialysate flow (QD) 800 ml/min] with a conventional high-flux dialyser of the same surface area in haemodialysis (HD) (QD 500 ml/min) and post-dilution HDF (at QS 60, QD = 500 ml/min and at QS 100, QD = 800 ml/min) modes. Subsequently, we performed an initial clinical application of the new device in six mid-dilution HDF treatments of five end-stage renal disease patients (QB 400 ml/min, QS 200 ml/min, QD 800 ml/min, treatment duration 205+/-23 min). RESULTS: In vitro urea and beta2-microglobulin clearances in mid-dilution HDF were, respectively, 309.2+/-5.5 and 144.4+/-15.2 ml/min (QS 100) and 321.6+/-4.1 and 204.9+/-4.1 ml/min (QS 200), compared with 278.6+/- 17.2 and 94.0+/-7.6 ml/min in HD, and 310.8+/-10.2 and 123.0+/-6.5 ml/min (QS 60) and 323.6+/-11.2 and 158.0+/-10.3 ml/min (QS 100) in post-dilution HDF. The in vivo trials showed the clinical utility of the device and confirmed the in vitro data: urea and beta2-microglobulin clearances were, respectively, 324.6+/- 10.9 and 207.9+/-29.3 ml/min, while reduction ratios were 75.0+/-5.5 and 83.6+/-4.7%. CONCLUSION: Our preliminary results need confirmation in a prospective cross-over study. However, the Nephros MD 190 haemodiafilter promises to be a true technological step ahead in terms of improved beta2-microglobulin removal.

Adult↗